In recent years there has been a substantial investment in research to create dexterous, multi- functional, prosthetic limbs for restoration of upper limb function following amputation. The focus on prosthetic limb development has, has in many ways, been fueled by advances in clinically operational motor neural- machine-interfaces; such as Targeted Reinnervation, the surgical redirection of amputated nerves for motor control of multifunction limbs, and other brain and peripheral neural-machine-interfaces on the near horizon. Although these motor interfaces provide considerable advantage to the control of the new prosthetic limbs, which are wonders of modern engineering, a fundamental problem still remains. Without natural and intuitive sensory feedback artificial limbs are still just insensate tools. Proprioception is the basic ability to sense where your arm is in space without looking. Amputees lack this sensory feedback, and this is the fundamental challenge in the implementation of advanced prosthetic limbs. Vision confirmation is needed for an amputee to use a prosthesis; from the most basic device to the most advanced. This is the key issue that we seek to address with our research objectives. We propose to attack the problem of prosthetic limbs that lack kinesthetic feedback in 3 Aims focused on developing and implementing approaches to harness and utilize a cognitive illusion of limb movement in human amputees with targeted sensory reinnervation. This research is important to the NIH scientific enterprise because it is highly translational and results directly impact amputee care. We hypothesize that we can stimulate the appropriate sensory receptors in the reinnervated tissue of targeted reinnervation amputees to generate the kinesthetic illusion and provide a sense of physiologically relevant limb movement for prosthetic limbs. Aim 1) We will use vibration and pressure to selectively activate the illusion and look at how targeted reinnervation amputees perceive this kinesthetic input. Aim 2) We will develop a small wearable robotic interface to selectively activate the kinesthetic receptors and assign sensations of limb movement to a prosthesis. With this we will look at how the subject interprets joint angle from a neutrally connected but physically unattached prosthesis. We will evaluate limb function with psychophysical examination of internal dynamic models related to constant velocity movements. We will also evaluate function using eye tracking and motion capture to track visual loading during prosthesis use. Aim 3) The prosthetic socket is the physical junction between the prosthesis and the amputee. This junction will need to evolve to reflect implementation restraints of the robot interface. To address this we will develop new socket designs to provide a limb movement feedback system with clinical applicability. PUBLIC HEALTH RELEVANCE: This research is relevant to public health because it is highly translational and the results will likely directly impact standard of care for amputees. As of 2011 there were 770,000 traumatic upper limb amputees in the US; a population that is young and active and will benefit substantially from more functional artificial arms that are neutrally integrated and provide a physiologically relevant sense of limb movement. Furthermore, our lines of investigation into neural interfaces and cognitive mechanisms of sensory feedback could provide far reaching scientific insight into challenges arising from sensory integration issues in many different fields.